Review
Endocrinology & Metabolism
Sarah Hamidi, Marie-Claude Hofmann, Priyanka C. C. Iyer, Maria E. E. Cabanillas, Mimi I. I. Hu, Naifa L. L. Busaidy, Ramona Dadu
Summary: The treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has seen significant advancements in the past decade, leading to a paradigm shift in patient management and prognosis. Improved understanding of tumor molecular drivers and access to next generation sequencing have resulted in the development and FDA-approval of targeted therapies for RR-DTCs, including multikinase inhibitors and fusion-specific kinase inhibitors. However, current treatments are not curative, and research efforts are focused on identifying and overcoming resistance mechanisms to tyrosine kinase inhibitors.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Oncology
Jingtai Zhi, Jiaoyu Yi, Xiukun Hou, Wei Wang, Weiwei Yang, Linfei Hu, Jianfeng Huang, Shicheng Guo, Xianhui Ruan, Ming Gao, Xiangqian Zheng
Summary: In this study, RTKs activation was found to lead to reactivation of the MAPK pathway and resistance to MEKi in differentiated thyroid carcinoma, which was reversed by SHP2 blockade. Combination therapy with SHP099, a novel active inhibitor of SHP2, and MEKi showed promising therapeutic effects for advanced thyroid carcinoma and MEKi-resistant cases.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Oncology
Chihiro Matsuyama, Tomohiro Enokida, Yuri Ueda, Shinya Suzuki, Takao Fujisawa, Kazue Ito, Susumu Okano, Makoto Tahara
Summary: In patients with radioiodine-refractory differentiated thyroid cancer, planned drug holidays for lenvatinib were found to be associated with significantly longer progression-free survival, time to treatment failure, and overall survival compared to daily oral administration, as well as lower levels of intolerable toxicity.
FRONTIERS IN ONCOLOGY
(2023)
Article
Medicine, General & Internal
Chung-Shien Lee, Emily Miao, Kasturi Das, Nagashree Seetharamu
Summary: A patient with a rare BRAF gene mutation (T599_V600insT) in thyroid carcinoma was treated with a combination of BRAF and MEK inhibitors. This mutation increases kinase activity, suggesting that these inhibitors could be an effective treatment option.
Article
Endocrinology & Metabolism
Pia Adam, Stefan Kircher, Iuliu Sbiera, Viktoria Florentine Koehler, Elke Berg, Thomas Knoesel, Benjamin Sandner, Wiebke Kristin Fenske, Hendrik Blaeker, Constantin Smaxwil, Andreas Zielke, Bence Sipos, Stephanie Allelein, Matthias Schott, Christine Dierks, Christine Spitzweg, Martin Fassnacht, Matthias Kroiss
Summary: High tumoral expression of PD-L1 in a large proportion of ATCs and a subgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFR expression is generally low in thyroid tumor cells. No impact of PD-L1 and FGFR 1-4 expression was observed on disease specific survival. The clinically observed synergism of PEM with LEN may be caused by immune modulation.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Marcia S. Brose, Yury Panaseykin, Bhavana Konda, Christelle de la Fouchardiere, Brett G. M. Hughes, Andrew G. Gianoukakis, Young Joo Park, Ilia Romanov, Monika K. Krzyzanowska, Sophie Leboulleux, Terri A. Binder, Corina Dutcus, Ran Xie, Matthew H. Taylor
Summary: This study compared the efficacy and toxicity of lenvatinib starting at doses of 24 mg/day and 18 mg/day in patients with RR-DTC. The results showed that the objective response rate was 57.3% in the 24 mg/day arm and 40.3% in the 18 mg/day arm, indicating that the starting dose of 18 mg/day did not demonstrate noninferiority. However, there was no clinically relevant difference in the safety profile between the two arms.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Bora Lim, Christine B. Peterson, Alexander Davis, Elin Cho, Troy Pearson, Huey Liu, Minha Hwang, Naoto Tada Ueno, Jangsoon Lee
Summary: The study showed that a combination therapy of ONC201 with MEK inhibitor can effectively inhibit the growth of triple-negative breast cancer cell lines, with ClpP levels correlating with ONC201 efficacy. Three-dimensional RNA interference screening identified MAPK and PI3K/Akt pathways as potential synergistic therapeutic partners.
Article
Endocrinology & Metabolism
Anna Koot, Rosella Hermens, Petronella Ottevanger, Romana Netea-Maier, Peep Stalmeier
Summary: This study developed evidence-based patient decision aids (PtDAs) for patients with differentiated thyroid cancer (DTC) to assist in two different treatment decisions. The PtDAs were well accepted and found to be helpful in decision-making, with the majority of participants recommending their use.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Oncology
Yuma Shibutani, Kazuko Tajiri, Shinya Suzuki, Tomohiro Enokida, Atsunobu Sagara, Susumu Okano, Takao Fujisawa, Fumiaki Sato, Tetsuro Yumoto, Motohiko Sano, Toshikatsu Kawasaki, Makoto Tahara
Summary: This study aimed to investigate the trend of hypertension after initiation of lenvatinib and the effectiveness of antihypertensive treatment. The study found that lenvatinib-induced hypertension occurs the day after administration, and higher baseline blood pressure is a significant risk factor for developing severe hypertension.
Review
Oncology
Alex Chambers, Madappa Kundranda, Santosh Rao, Fade Mahmoud, Jiaxin Niu
Summary: The combination of anti-angiogenesis and immunotherapy is supported by strong rationale and clinical evidence, overcoming immunotherapy resistance and providing a more robust treatment option. This combination therapy has become a standard of care for some tumor types and is expected to expand to more tumor types in the future.
CURRENT ONCOLOGY REPORTS
(2021)
Article
Endocrinology & Metabolism
Yan-Song Lin, Xin Zhang, Chen Wang, Yan-Qing Liu, Wen-Min Guan, Jun Liang
Summary: The long-term evaluation of apatinib in patients with radioiodine refractory differentiated thyroid cancer showed sustainable efficacy and tolerable safety profile, especially for patients with BRAF(V600E) mutation.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Oncology
Christelle de la Fouchardiere, Yann Godbert, Cecile Dalban, Frederic Illouz, Johanna Wassermann, Christine Do Cao, Stephane Bardet, Slimane Zerdoud, Cecile N. Chougnet, Mohamed Zalzali, Danielle Benisvy, Patricia Niccoli, Laurence Digue, Livia Lamartina, Paul Schwartz, Francoise Borson Chazot, Julien Gautier, David Perol, Sophie Leboulleux
Summary: The study investigated the efficacy of intermittent versus continuous pazopanib administration in RAIR-TC patients, showing no significant difference in efficacy or tolerance between the two treatment approaches.
EUROPEAN JOURNAL OF CANCER
(2021)
Review
Oncology
Lingyu Li, Lin Cheng, Ri Sa, Xian Qiu, Libo Chen
Summary: Several tyrosine kinase inhibitors have been approved for treating advanced thyroid cancer and real-world studies have shown their long-term efficacy and safety.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Article
Oncology
Dirk Schadendorf, Caroline Robert, Reinhard Dummer, Keith T. Flaherty, Hussein A. Tawbi, Alexander M. Menzies, Hiya Banerjee, Mike Lau, Georgina V. Long
Summary: Pyrexia is a common adverse event in patients treated with dabrafenib plus trametinib, with 61.3% of patients experiencing it in clinical trials. The incidence of pyrexia is highest early in treatment and decreased with time on treatment. Temporary dose interruption of dabrafenib or trametinib was found to be the most common and effective management strategy for pyrexia.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Oncology
Chia-Chia Liu, Jamunarani Veeraraghavan, Ying Tan, Jin-Ah Kim, Xian Wang, Suet Kee Loo, Sanghoon Lee, Yiheng Hu, Xiao-Song Wang
Summary: A novel tumor-specific chimeric transcript RAD51AP1-DYRK4 was identified in luminal B breast tumors, with its overexpression associated with aggressiveness. Ectopic expression of RAD51AP1-DYRK4 activated the MEK/ERK pathway, enhancing cell motility and sensitivity to MEK inhibitors. This discovery may lead to new therapeutic opportunities for aggressive breast tumors overexpressing RAD51AP1-DYRK4 fusion.
CLINICAL CANCER RESEARCH
(2021)
Editorial Material
Oncology
Ben George, Razelle Kurzrock
Article
Oncology
Claire F. Friedman, John D. Hainsworth, Razelle Kurzrock, David R. Spigel, Howard A. Burris, Christopher J. Sweeney, Funda Meric-Bernstam, Yong Wang, Jonathan Levy, Jessica Grindheim, David S. Shames, Katja Schulze, Arisha Patel, Charles Swanton
Summary: Atezolizumab monotherapy showed promising clinical activity in patients with TMB >= 16 mut/Mb tumors lacking other suitable treatment options and who were immunotherapy-naive at enrollment, regardless of microsatellite instability status. Limited activity was observed in tumors with TMB >= 10 and < 16 mut/Mb.
Article
Oncology
Amlie Boichard, Razelle Kurzrock
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Oncology
Diviya Gupta, Razelle Kurzrock, Suzanna Lee, Ryosuke Okamura, Hyo Jeong Lim, Ki Hwan Kim, Jason K. Sicklick, Shumei Kato
Summary: This study evaluated the impact of N-of-One therapeutic strategies on the outcome of patients with only one genomic alteration or alterations in one oncogenic pathway. The results showed that a subset of cancer patients may benefit from customized therapeutic matching.
NPJ PRECISION ONCOLOGY
(2022)
Article
Oncology
Shumei Kato, Sophia Gumas, Jacob J. Adashek, Ryosuke Okamura, Suzanna Lee, Jason K. Sicklick, Razelle Kurzrock
Summary: Carcinoma of unknown primary (CUP) is a challenging malignancy to manage. This study assessed the multi-omic profiles and treatment outcomes of CUP based on the degree of precision matching. The results showed that treatments with high degrees of matching to molecular alterations were associated with improved outcomes.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Rushikesh S. Joshi, Amelie Boichard, Jacob J. Adashek, Razelle Kurzrock
Summary: Tumors with TP53 mutations show higher tumor amplification burden, with amplifications potentially being secondary consequences of TP53 mutations.
CANCER BIOLOGY & THERAPY
(2022)
Review
Oncology
Ruchi P. Agashe, Scott M. Lippman, Razelle Kurzrock
MOLECULAR CANCER THERAPEUTICS
(2022)
Review
Genetics & Heredity
Elena Fountzilas, Apostolia M. Tsimberidou, Henry Hiep Vo, Razelle Kurzrock
Summary: Recent breakthroughs in biotechnology have allowed for the identification of unique molecular features that drive malignancies. Precision medicine has used next-generation sequencing and matched targeted therapy/immunotherapy to transform the outlook for fatal cancers. Multiple trial designs and personalized combination treatment strategies have been implemented to accelerate drug evaluation and individualized treatment.
Article
Oncology
Jason J. Luke, Marwan Fakih, Charles Schneider, E. Gabriela Chiorean, Johanna Bendell, Rebecca Kristeleit, Razelle Kurzrock, Sarah P. Blagden, Irene Brana, Laura W. Goff, Kevin O'Hayer, Ryan Geschwindt, Michael Smith, Feng Zhou, Aung Naing
Summary: This study aimed to evaluate the clinical benefits of epigenetic therapy plus IDO1 inhibition and immune checkpoint blockade in patients with advanced solid tumors. The findings showed that although the treatment was well tolerated, it did not result in substantial clinical response in patients previously exposed to immunotherapy.
BRITISH JOURNAL OF CANCER
(2023)
Editorial Material
Oncology
Vivek Subbiah, Razelle Kurzrock
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Letter
Oncology
Vivek Subbiah, Razelle Kurzrock
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Umut Disel, Smruthy Sivakumar, Tim Pham, Zoe Fleischmann, R. Anu, Ethan S. Sokol, Razelle Kurzrock
Summary: The aim of this study was to identify the prevalence of MUTYH alterations across different cancer types and investigate the relationship between MUTYH mutations and actionable biomarkers. The research utilized a comprehensive genomic dataset of patients with solid tumors, finding that 2.8% of the tumors had MUTYH alterations, with 55% predicted to be germline mutations. MUTYH-altered cancers showed higher tumor mutational burden and more frequent KRAS G12C alterations, particularly in colorectal cancer. PD-L1 expression levels were not associated with MUTYH alteration status. Computational analysis revealed that MUTYH mutational signatures were linked to higher hydrophobicity, indicating potential immunogenicity of neoantigens. Survival rates were similar between patients with MUTYH-altered and wild-type tumors. Overall, the study suggests that pharmacological targeting of specific biomarkers and immunogenicity may be effective in treating MUTYH-mutated malignancies.
Article
Genetics & Heredity
Hirotaka Miyashita, Razelle Kurzrock, Nicholas J. Bevins, Kartheeswaran Thangathurai, Suzanna Lee, Sarabjot Pabla, Mary Nesline, Sean T. Glenn, Jeffrey M. Conroy, Paul DePietro, Eitan Rubin, Jason K. Sicklick, Shumei Kato
Summary: Immune checkpoint blockade is effective for only a subset of cancers. Targeting T-cell priming markers (TPMs) may enhance activity. This study analyzed the transcriptomics of 15 TPMs in a pan-cancer cohort and found diverse expression patterns of TPMs independent of histological type but correlating with other immunotherapy biomarkers. Individualized selection of patients based on TPM immunomic profiles may potentially help with immunotherapy optimization.
NPJ GENOMIC MEDICINE
(2023)
Review
Oncology
Vivek Subbiah, Howard A. Burris III, Razelle Kurzrock
Summary: Advances in next-generation sequencing, targeted therapies, and immunotherapies have transformed cancer therapy. Basket trials, an effective clinical trial design, evaluate the efficacy of therapies based on specific molecular alterations across multiple cancer types, offering potential for personalized treatments and revolutionizing cancer care.
Article
Medicine, Research & Experimental
Juan Pablo Hinestrosa, Razelle Kurzrock, Jean M. Lewis, Nicholas J. Schork, Gregor Schroeder, Ashish M. Kamat, Andrew M. Lowy, Ramez N. Eskander, Orlando Perrera, David Searson, Kiarash Rastegar, Jake R. Hughes, Victor Ortiz, Iryna Clark, Heath I. Balcer, Larry Arakelyan, Robert Turner, Paul R. Billings, Mark J. Adler, Scott M. Lippman, Rajaram Krishnan
Summary: This study developed an EV-based blood biomarker classifier utilizing machine learning algorithm to detect early-stage pancreatic, ovarian, and bladder cancer. The results showed high sensitivity and specificity of this classifier in early cancer detection, indicating its potential clinical value for further studies.
COMMUNICATIONS MEDICINE
(2022)